scholarly journals Is Focal Cortical Dysplasia/Epilepsy Caused by Somatic MTOR Mutations Always a Unilateral Disorder?

2020 ◽  
Vol 7 (1) ◽  
pp. e540
Author(s):  
Renzo Guerrini ◽  
Mara Cavallin ◽  
Tommaso Pippucci ◽  
Anna Rosati ◽  
Francesca Bisulli ◽  
...  
Keyword(s):  
Focal Cortical Dysplasia ◽  
Mammalian Target Of Rapamycin ◽  
Complete Removal ◽  
Cortical Dysplasia ◽  
Contralateral Hemisphere ◽  
Wide Margin ◽  
Intractable Seizures ◽  
The Brain ◽  
Time Of Origin ◽  
Brain Study

ObjectiveTo alert about the wide margin of unpredictability that distribution of somatic MTOR mosaicism may have in the brain and the risk for independent epileptogenesis arising from the seemingly healthy contralateral hemisphere after complete removal of epileptogenic focal cortical dysplasia (FCD).MethodsClinical, EEG, MRI, histopathology, and molecular genetics in 2 patients (1 and 2) treated with focal resections and subsequent complete hemispherectomy for epileptogenic FCD due to somatic MTOR mutations. Autoptic brain study of bilateral asymmetric hemispheric dysplasia and identification of alternative allele fraction (AAF) rates for AKT1 (patient 3).ResultsThe strongly hyperactivating p.Ser2215Phe (patient 1) and p.Leu1460Pro (patient 2) MTOR mutations were at low-level AAF in the dysplastic tissue. After repeated resections and eventual complete hemispherectomy, both patients manifested intractable seizures arising from the contralateral, seemingly healthy hemisphere. In patient 3, the p.Glu17Lys AKT1 mutation exhibited random distribution and AAF rates in different tissues with double levels in the more severely dysplastic cerebral hemisphere.ConclusionsOur understanding of the distribution of somatic mutations in the brain in relation to the type of malformation and its hypothesized time of origin may be faulty. Large studies may reveal that the risk of a first surgery being disappointing might be related more to the specific somatic mammalian target of rapamycin mutation identified than to completeness of resection and that the advantages of repeated resections after a first unsuccessful operation should be weighed against the risk of the contralateral hemisphere becoming in turn epileptogenic.

Utility of depth electrode placement in the neurosurgical management of bottom-of-sulcus lesions: technical note

2019 ◽  
Vol 24 (3) ◽  
pp. 284-292
Author(s):  
Eisha A. Christian ◽  
Elysa Widjaja ◽  
Ayako Ochi ◽  
Hiroshi Otsubo ◽  
Stephanie Holowka ◽  
...  
Keyword(s):  
Pediatric Patients ◽  
Focal Cortical Dysplasia ◽  
Target Identification ◽  
Cortical Dysplasia ◽  
Technical Note ◽  
Electrode Placement ◽  
Electrode Implantation ◽  
Depth Electrodes ◽  
Intracranial Electrode ◽  
The Brain

OBJECTIVESmall lesions at the depth of the sulcus, such as with bottom-of-sulcus focal cortical dysplasia, are not visible from the surface of the brain and can therefore be technically challenging to resect. In this technical note, the authors describe their method of using depth electrodes as landmarks for the subsequent resection of these exacting lesions.METHODSA retrospective review was performed on pediatric patients who had undergone invasive electroencephalography with depth electrodes that were subsequently used as guides for resection in the period between July 2015 and June 2017.RESULTSTen patients (3–15 years old) met the criteria for this study. At the same time as invasive subdural grid and/or strip insertion, between 2 and 4 depth electrodes were placed using a hand-held frameless neuronavigation technique. Of the total 28 depth electrodes inserted, all were found within the targeted locations on postoperative imaging. There was 1 patient in whom an asymptomatic subarachnoid hemorrhage was demonstrated on postprocedural imaging. Depth electrodes aided in target identification in all 10 cases.CONCLUSIONSDepth electrodes placed at the time of invasive intracranial electrode implantation can be used to help localize, target, and resect primary zones of epileptogenesis caused by bottom-of-sulcus lesions.

scholarly journals Dual Pathology in Rasmussen’s Encephalitis: A Report of Coexistent Focal Cortical Dysplasia and Review of the Literature

2012 ◽  
Vol 2012 ◽  
pp. 1-4 ◽  
Author(s):  
Richard A. Prayson
Keyword(s):  
Chronic Inflammation ◽  
Focal Cortical Dysplasia ◽  
Intractable Epilepsy ◽  
Cortical Dysplasia ◽  
Cortical Atrophy ◽  
Review Of The Literature ◽  
Dual Pathology ◽  
Rasmussen’S Encephalitis ◽  
Intractable Seizures

Rasmussen’s encephalitis is a well-established, albeit rare cause of medically intractable epilepsy. In a small number of Rasmussen's cases, a second pathology is identified, which independently can cause medically intractable seizures (dual pathology). This paper documents a case of a 13-year-old male who presented with medically intractable epilepsy. The patient underwent a series of surgical resections, early on resulting in a diagnosis of focal cortical dysplasia and later yielding a diagnosis of coexistent Rasmussen’s encephalitis, marked by chronic inflammation, microglial nodules, and focal cortical atrophy, combined with focal cortical dysplasia (Palmini et al. type IIA, ILAE type IIA). The literature on dual pathology in the setting of Rasmussen’s encephalitis is reviewed.

scholarly journals DEPDC5 variant in focal cortical dysplasia: a case report and review of the literature

2021 ◽  
Vol 2021 (5) ◽  
Author(s):  
Joana Jesus-Ribeiro ◽  
Cristina Pereira ◽  
Conceição Robalo ◽  
Daniela J Pereira ◽  
Diana Duro ◽  
...  
Keyword(s):  
Focal Epilepsy ◽  
Focal Cortical Dysplasia ◽  
Mammalian Target Of Rapamycin ◽  
Mtor Inhibitors ◽  
Missense Variant ◽  
Cortical Dysplasia ◽  
Negative Regulator ◽  
Missense Variants ◽  
Borderline Intellectual Functioning ◽  
Unknown Significance

ABSTRACT Germline and 2-hit brain somatic variants in DEPDC5 gene, a negative regulator of the mammalian target of rapamycin (mTOR) pathway, are increasingly recognized in patients with focal cortical dysplasia (FCD). Next-generation targeted sequencing identified a heterozygous germline variant in DEPDC5 gene (c.3241A>C, p.Thr1081Pro), classified as of unknown significance, in a patient with clinical features compatible with DEPDC5 phenotype (FCD, focal epilepsy, attention-deficit/hyperactivity disorder and borderline intellectual functioning). This missense variant has previously been reported in two other epileptic patients. Although interpretation of missense variants remains a challenge, DEPDC5 variants in patients with FCD and epilepsy cannot be neglected. Null variants were the most frequently reported in FCD patients, but missense variants have been described as well. The recognition of DEPDC5 phenotype and the appropriate interpretation of the detected variants are essential, since it may have important treatment implications in the near future, namely the use of mTOR inhibitors.

Curved Planar Reconstruction of MR Images in Focal Cortical Dysplasia of the Brain

2002 ◽  
Vol 46 (6) ◽  
pp. 529
Author(s):  
Gyung Ho Chung ◽  
Sang Yong Lee ◽  
Chong Soo Kim ◽  
Young Kon Kim ◽  
Young Hwan Lee ◽  
...  
Keyword(s):  
Focal Cortical Dysplasia ◽  
Cortical Dysplasia ◽  
Mr Images ◽  
Curved Planar Reconstruction ◽  
The Brain

Special MRI protocol of the brain imaging with higher sensitivity to the focal cortical dysplasia

2013 ◽  
Vol 44 (S 01) ◽  
Author(s):  
M Kyncl ◽  
A Jahodova ◽  
B Prosova ◽  
P Krsek ◽  
Z Svata ◽  
...  
Keyword(s):  
Brain Imaging ◽  
Focal Cortical Dysplasia ◽  
Cortical Dysplasia ◽  
Mri Protocol ◽  
The Brain ◽  
Higher Sensitivity

Using a recurrent neural network with S2 characteristics, efficient identification of localised cortical dysplasia

2021 ◽  
pp. 1-14
Author(s):  
A. Karthika ◽  
R. Subramanian ◽  
S. Karthik
Keyword(s):  
Neural Network ◽  
Recurrent Neural Network ◽  
Short Term Memory ◽  
Focal Cortical Dysplasia ◽  
Cortical Dysplasia ◽  
Support Vector ◽  
Sensitivity Rate ◽  
Long Short Term Memory ◽  
Artificial Neural Network Ann ◽  
The Brain

Focal cortical dysplasia (FCD) is an inborn anomaly in brain growth and morphological deformation in lesions of the brain which induces focal seizures. Neurosurgical therapies were performed for the detection of FCD. Furthermore, it can be overcome through the presurgical evaluation of epilepsy. The surgical result is attained basically through the output of the presurgical output. In preprocessing the process of increasing true positives with the decrease in false negatives occurs which results in an effective outcome. MRI (Magnetic Resonance Imaging) outputs are efficient to predict the FCD lesions through T1- MPRAGE and T2- FLAIR efficient output can be obtained. In our proposed work we extract the S2 features through the testing of T1, T2 images. Using RNN-LSTM (Recurrent neural network-Long short-term memory) test images were trained and the FCD lesions were segmented. The output of our work is compared with the proposed work yields better results compared to the existing system such as artificial neural network (ANN), support vector machine (SVM), and convolution neural network (CNN). This approach obtained an accuracy rate of 0.195% (ANN), 0.20% (SVM), 0.14% (CNN), specificity rate of 0.23% (ANN), 0.15% (SVM), 0.13% (CNN) and sensitivity rate of 0.22% (ANN), 0.14% (SVM), 0.08% (CNN) respectively in comparison with RNN-LSTM.

scholarly journals Somatic double-hit in MTOR and RPS6 in hemimegalencephaly with intractable epilepsy

2019 ◽  
Vol 28 (22) ◽  
pp. 3755-3765 ◽  
Author(s):  
Cristiana Pelorosso ◽  
Françoise Watrin ◽  
Valerio Conti ◽  
Emmanuelle Buhler ◽  
Antoinette Gelot ◽  
...  
Keyword(s):  
Brain Tissue ◽  
Focal Cortical Dysplasia ◽  
Mammalian Target Of Rapamycin ◽  
Somatic Mosaicism ◽  
Intractable Epilepsy ◽  
Cortical Dysplasia ◽  
Mtor Pathway ◽  
Activating Mutations ◽  
Severe Intellectual Disability ◽  
Double Hit

Abstract Single germline or somatic activating mutations of mammalian target of rapamycin (mTOR) pathway genes are emerging as a major cause of type II focal cortical dysplasia (FCD), hemimegalencephaly (HME) and tuberous sclerosis complex (TSC). A double-hit mechanism, based on a primary germline mutation in one allele and a secondary somatic hit affecting the other allele of the same gene in a small number of cells, has been documented in some patients with TSC or FCD. In a patient with HME, severe intellectual disability, intractable seizures and hypochromic skin patches, we identified the ribosomal protein S6 (RPS6) p.R232H variant, present as somatic mosaicism at ~15.1% in dysplastic brain tissue and ~11% in blood, and the MTOR p.S2215F variant, detected as ~8.8% mosaicism in brain tissue, but not in blood. Overexpressing the two variants independently in animal models, we demonstrated that MTOR p.S2215F caused neuronal migration delay and cytomegaly, while RPS6 p.R232H prompted increased cell proliferation. Double mutants exhibited a more severe phenotype, with increased proliferation and migration defects at embryonic stage and, at postnatal stage, cytomegalic cells exhibiting eccentric nuclei and binucleation, which are typical features of balloon cells. These findings suggest a synergistic effect of the two variants. This study indicates that, in addition to single activating mutations and double-hit inactivating mutations in mTOR pathway genes, severe forms of cortical dysplasia can also result from activating mutations affecting different genes in this pathway. RPS6 is a potential novel disease-related gene.

scholarly journals Neuronal Migration Disorders: A Contribution of Modern Neuroimaging to the Etiologic Diagnosis of Epilepsy

1991 ◽  
Vol 18 (S4) ◽  
pp. 580-587 ◽  
Author(s):  
André Palmini ◽  
Frederick Andermann ◽  
André Olivier ◽  
Donatella Tampieri ◽  
Yvon Robitaille ◽  
...  
Keyword(s):  
Neuronal Migration ◽  
Focal Cortical Dysplasia ◽  
Cortical Dysplasia ◽  
Dysplastic Lesion ◽  
Surgical Strategies ◽  
Intractable Seizures ◽  
Neuronal Migration Disorders ◽  
Double Cortex Syndrome ◽  
Double Cortex ◽  
Migration Disorders

ABSTRACT:Computed tomography and magnetic resonance imaging enable the identification of neuronal migration disorders during life. Several specific syndromes have been identified and early diagnosis of previously unrecognized entities is now possible. We report 51 patients with imaging. Thirty-two had a single widespread cortical dysplastic lesion. Twenty-eight had focal corticectomies. From a pathological standpoint, these encompassed focal cortical dysplasia (14 cases) and forme fruste of tuberous sclerosis (10 cases). These two groups of patients were indistinguishable from the clinical and radiological standpoint. In only two was the MRI examination normal. In addition, there were 10 with bilateral perisylvian dysplasia, four with diffuse cortical dysplasia or the "double cortex" syndrome, three with hemimegalencephaly, one with megalencephaly, and one with nodular neuronal heterotopia. The electroclinical and imaging findings led to the development of specific surgical strategies for the alleviation of the intractable seizures in each of these radiologically-defined syndromes.

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